The CLL Research Consortium (CRC) is multi-institutional program, investigating the biologic basis of CLL and novel biologic and pharmacologic treatments for this disease, which enables CRC investigators to function beyond the capacities of any single member. It provides for uniform, high-volume sample accrual to a sophisticated national tissue bank, secured on-line information systems, and an infrastructure that facilitates the research on novel therapies and the evaluation of clinical-laboratory relationships that improve clinical staging and/or that assist in the early assessment of response to novel therapies. The CRC has six major projects. Project 1 investigates the genetic basis for CLL and the development of novel probes that can translate genetic discoveries into the clinic. Project 2 investigates the leukemia cell expression of proteins that regulate susceptibility to apoptosis and novel compounds that can interfere with their biochemical function. Project 3 examines for leukemia-associated antigens and novel techniques for active immunotherapy of this disease, including gene therapy. Project 4 examines the mechanism(s) accounting for ineffective T cell mediated immune response against putative leukemia-cell antigens and evaluates for specific T cell defects that can interfere with development of effective anti-tumor cellular immune responses. Project 5 focuses on promising anticancer agents for phase l/ll testing in patients with CLL and examines the activity of these agents acting alone or in mechanism-based combinations. Project 6 is a new project that examines the pharmacology of promising new agents for treatment of this disease. The CRC has 4 cores: The administrative core coordinates research investigations, oversees the generation and maintenance of the clinical and laboratory databases and information systems, and facilitates information and data exchange between program participants. The Biostatistics Core assists investigators in the design and interpretation of basic and clinical research. The Tissue Core is responsible for tissue banking, sample trafficking, and leukemia-sample laboratory testing and sample-validation. The Clinical Core helps develop, implement, execute, monitor, and analyze CRC clinical trials.